Nuclear-Targeting Gold Nanorods for Extremely Low NIR Activated Photothermal Therapy

Photorelated nanomedicine is of particular interest as an emerging paradigm toward precise cancer therapy, as demonstrated by recent developments of photothermal therapy (PTT), an emerging technique employing light-converting agents to burn cancerous cells by overdosed optical energy-converted heat. However, most of the laser irradiations needed for effective PTT significantly exceed the maximal permissible power density in human skin, which is likely to damage surrounding normal tissues. Herein, we report a strategy of intranuclear PTT of cancer enabled by nuclear-targeted delivery of gold nanorods of ∼10.5 × 40.5 nm in size via conjugation with nuclear location signal peptides (GNRs-NLS) under an extremely low near-infrared irradiation of 0.2 W/cm², much below the maximal permissible exposure of skin. Interestingly, we found that a mild but nuclear-focused temperature increase generated by GNRs-NLS is sufficient to cause damage to intranuclear DNA and the inhibition of DNA repair process, which, interestingly, led to the cancer cell apoptosis rather than to conventional cell necrosis by thermal ablation during PTT. Correspondingly, tumors treated with GNRs-NLS exhibited gradual but significant regressions rather than traditional harsh burning-up of tumors, in comparison with negligible antitumor effect by GNRs without nuclear targeting under the same ultralow NIR irradiation. This report demonstrates the successful intranuclear efficient photothermal therapy of cancer via cell apoptosis by photoadsorbing agents, e.g., GNRs-NLS in the present case, with largely mitigated side-effect on normal tissues and therefore substantially improved biosafety.